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Clinical Pharmacokinetics of Artemether and Lumefantrine (Riamet®)

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Abstract

This paper reports the clinical pharmacokinetics of artemether and lumefantrine in healthy volunteers and in malaria patients. These two drugs are the active components of the fixed-dose oral combination tablet co-artemether (Riamet®), used for the treatment of Plasmodium falciparum malaria.

Artemether has a fast absorption rate followed by rapid clearance from plasma [terminal elimination half-life (t1/2β) 2 to 3 hours]. Its major metabolite dihydroartemisinin (DHA) is formed rapidly and has a similar clearance pattern to artemether. Lumefantrine is slowly absorbed (2 hours lag time) followed by a slow clearance from plasma (t1/2β up to 10 days). Food intake significantly increases the bioavailability of both artemether (>2-fold) and lumefantrine (approximately 16-fold).

Artemether and lumefantrine are predominantly metabolised by the cytochrome P450 3A4 (CYP3A4) isoenzyme. The intersubject variability for artemether, DHA and lumefantrine is high in both healthy volunteers and patients.

CYP3A4 substrates/inhibitors such as the antimalarial mefloquine can be coadministered with co-artemether without clinically relevant risk of drug-drug interaction. Similarly, potential for a significant medical hazard in the management of P. falciparum malaria with co-artemether following co-administration in close temporal relationship with quinine (a CYP3A4 substrate) is unlikely. The wide therapeutic index of artemether and lumefantrine and the short duration of administration of co-artemether suggest that the risk for any tolerability problems from drug accumulation is minimal.

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  1. Novartis Pharma AG, Clinical Pharmacology, WSJ-27.7.029, CH-4002, Basel, Switzerland

    Gilbert Lefèvre & Mikael S. Thomsen

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  1. Gilbert Lefèvre
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Correspondence to Gilbert Lefèvre.

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Lefèvre, G., Thomsen, M.S. Clinical Pharmacokinetics of Artemether and Lumefantrine (Riamet®). Clin. Drug Investig. 18, 467–480 (1999). https://doi.org/10.2165/00044011-199918060-00006

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